Interactive homeostatic mechanisms exist between cells from the time of blastula formation. These regulatory processes are usually able to maintain tissue integrity through all phases of life and can be regarded as mechanisms of "non-immune surveillance" against neoplasia. Immune mechanisms for surveillance also exist, but little is known of how non-immune and immune surveillance might interface to control the emergence of malignant growths. Normal mammary gland tissue interactions occur in the embryo and continue through puberty, child bearing, and menopause. A progression of tissue interactions occurs from the 11 day (in utero) fetal mammary bud to the aberrant tissues of malignant tumors. I have demonstrated that mammary tumor growth is augmented by normal mammary gland tissues in the mouse and that the mechanism of that site preference is probably not due to the immunologically privileged nature of the fatpad. I have also shown that, despite the preference of the tumor cells for the mammary site, metastatic tumor cells metastasize more readily from the fatpad than the subcutis. I wish to continue my investigations of mammary tumors growing in their natural anatomic site to determine both the mechanism of the site preference and its consequences. The study of the mechanism will continue to focus on cellular interactions within the mammary gland fatpad. Interactions between tumor cells and non-lymphoid cells (normal glandular tissue, preneoplastic lesions, and other tumors), between tumor and lymphoid cells, and between lymphoid and non-lymphoid cells of the mammary gland will be investigated both in vitro and in vivo. The studies of the consequences will focus on the affect of mammary gland tissue interactions on progression. Eventually, manipulation of tissue interactions could lead to new therapeutic strategies.